POS1039 DEUCRAVACITINIB, AN ORAL, SELECTIVE TYROSINE KINASE 2 INHIBITOR, IN A PHASE 2 TRIAL IN PSORIATIC ARTHRITIS: ACHIEVEMENT OF MINIMAL DISEASE ACTIVITY AND ITS COMPONENTS
Authors: A. Kavanaugh, L. Coates, J. F. Merola, P. J. Mease, M. Nowak, S. Banerjee, L. Hippeli, T. Lehman
Journal: Annals of the Rheumatic Diseases (2022)

Background Tyrosine kinase 2 (TYK2) is an intracellular kinase in the Janus kinase (JAK) family that mediates the signalling of multiple cytokines, including those central to the immunopathogenesis of psoriatic arthritis (PsA), such as IL-23. Deucravacitinib (DEUC) is a novel, oral, selective, allosteric inhibitor of TYK2 that acts by binding to the unique regulatory domain on the enzyme. In a Phase 2 trial in patients with active PsA, DEUC was significantly more efficacious than placebo (PBO) after 16 weeks of treatment and was well tolerated. 1 Objectives This analysis further evaluated the effect of DEUC in this trial on achievement of individual components of minimal disease activity (MDA). Methods This double-blind, multicenter Phase 2 trial ( NCT03881059 ) enrolled patients (n=203) with a PsA diagnosis ≥6 months who fulfilled Classification Criteria for Psoriatic Arthritis at screening and had active joint disease (≥3 tender and ≥3 swollen joints), high-sensitivity C-reactive protein ≥3 mg/L, and ≥1 plaque psoriasis lesion (≥2 cm). Eligible patients had failed or were intolerant to ≥1 nonsteroidal anti-inflammatory, conventional synthetic DMARD, and/or 1 tumour necrosis factor inhibitor (≤30%). Patients were randomized 1:1:1 to receive PBO, DEUC 6 mg once daily (QD), or 12 mg QD. The percentage of patients achieving MDA (5/7: tender joint count [TJC] ≤1, swollen joint count [SJC] ≤1, tender entheseal points [TEP] ≤1, Patient Global Assessment of disease activity [PtGA] ≤20, Patient Global Assessment of pain [Pain] ≤15, Health Assessment Questionnaire-Disability Index [HAQ-DI] ≤0.5, and Psoriasis Area and Severity Index [PASI] ≤1 or body surface area [BSA] ≤3%) as well as proportions of patients achieving each of the MDA components in all patients, MDA responders, and nonresponders were assessed through Week 16. Results Of 203 patients randomized, 180 (89%) completed 16 weeks of treatment (PBO, 58/66 [88%]; DEUC 6 mg QD, 63/70 [90%]; DEUC 12 mg QD, 59/67 [88%]). Demographic and baseline disease characteristics were generally similar across groups. Although no patient had met 5 of 7 criteria required for achieving MDA at baseline, several individual components of MDA were met at baseline, most frequently TEP ≤1 (PBO, 57.6%; DEUC 6 mg QD, 64.3%; DEUC 12 mg QD, 65.7%). After 16 weeks of treatment, 7.6%, 22.9%, and 23.9% of patients in the PBO, DEUC 6 mg QD, and DEUC 12 mg QD groups, respectively, achieved MDA response. Treatment with DEUC was associated with a numerically greater mean reduction from baseline in all MDA components versus PBO over 16 weeks of treatment in all patients. At Week 16, more patients receiving DEUC versus PBO achieved the threshold for each of the MDA components (Figure 1). Conclusion In this study, patients treated with DEUC achieved a higher rate of MDA response compared with patients treated with PBO after 16 weeks of treatment. More patients receiving DEUC treatment achieved each of the MDA components compared with patients receiving PBO. References [1]Mease PJ et al. Efficacy and Safety of Selective TYK2 Inhibitor, Deucravacitinib, in a Phase 2 Trial in Psoriatic Arthritis. Ann Rheum Dis. (In Press). Acknowledgements This study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Julianne Hatfield, PhD at Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Bristol Myers Squibb. Disclosure of Interests Arthur Kavanaugh Grant/research support from: Clinical research sponsored by Abbott, Amgen, Janssen, and UCB, Laura Coates Speakers bureau: Has been paid as a speaker for AbbVie, Amgen, Biogen, Celgene, Gilead, Eli Lilly, Janssen, Medac, Novartis, Pfizer, and UCB., Consultant of: Worked as a paid consultant for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB., Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Pfizer, and Novartis, Joseph F. Merola Consultant of: Consultant and/or investigator: Amgen, AbbVie, Biogen, Bristol-Myers Squibb, Dermavant, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB., Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, UCB., Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, UCB, Miroslawa Nowak Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Subhashis Banerjee Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Lauren Hippeli Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Thomas Lehman Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb